In an opened randomized study of women undergoing in vitro fertilization with expected suboptimal response to controlled ovarian stimulation (Poseidon Group 2b) investigators will examine clinical efficacy and safety of two stimulation protocols: Corifollitropin alfa (Elonva) in combination with menotropin (Merional) versus Follitropin alfa and lutropin alfa (Pergoveris).
Patients, found eligible for the study, will be randomized (envelope method) into two arms in 1:1 ratio at the start of stimulation (menstrual cycle day 2-3, randomization day): Arm A - ovarian stimulation with Corifollitropin alfa in combination with menotropin; Arm B - ovarian stimulation with Follitropin alfa and lutropin alfa. At the first day of controlled ovarian stimulation (COS) participants in the first group will receive a single injection of Corifollitropin alfa 150 mcg followed by daily menotropin administration at the dose of 150 international unit (IU) from stimulation day 1 to day 7 and at the dose of 300 IU from day 8 up to the end of stimulation. Ovarian stimulation in group B will be performed with daily 300 IU of Follitropin alfa and lutropin alfa starting on menstrual cycle day 2-3. For all subjects, a fixed dose of gonadotropin-releasing hormone (GnRH) antagonist will be injected daily as soon as one of the follicles reaches the ≥14 mm diameter and stopped one day before oocyte pick up (OPU); ovulatory dose of human chorionic gonadotropin (hCG) could be administered when at least one follicle reaches 16.5 mm in diameter. Retrieved oocytes following fertilization (conventional IVF or ICSI) will be cultured to morula or blastocyst stage followed by ultrasound guided single or double embryo transfer (ET day, performed 4-5 days after OPU).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
32
Procedure: Ovarian stimulation is performed by the combination of a single Corifollitropin alfa 150 mcg injection on menstrual cycle day 2-3 and daily menotropin administration at the dose of 150 IU from stimulation day 1-7 and at the dose of 300 IU from day 8 to the end of stimulation (maximal dose adjustment to 450 IU). Other interventions: conventional GnRH antagonist protocol and in vitro fertilization (IVF/ICSI) cycle
Procedure: Ovarian stimulation is performed with daily 300 IU of Follitropin alfa and lutropin alfa starting on menstrual cycle day 2-3. Maximal allowed dose adjustment is 450 IU daily. Other interventions: conventional GnRH antagonist protocol and in vitro fertilization (IVF/ICSI) cycle.
D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology
Saint Petersburg, Russia
Number of cumulus-oocyte complexes (COCs)
Number of COCs, obtained during oocyte pick up (OPU), after controlled ovarian stimulation (COS) in two protocols
Time frame: 3-4 weeks after ET
Duration of stimulation
total days of COS: from the first gonadotropins administration to ovulation triggering
Time frame: 2-4 weeks after randomization
Number of follicles at the end of stimulation
measured for follicles ≥17 mm and ≥14 mm
Time frame: 2-4 weeks after randomization
Dose adjustment frequency
number of participants with menopausal or recombinant human follicle stimulating hormone (FSH) dose increase
Time frame: 2-4 weeks after randomization
Number of participants with optimal or suboptimal response to COS
≥ 5 COCs at at oocyte recovery day
Time frame: 2-4 weeks after randomization
Number of mature (MII) oocytes
assessment is done only for ICSI cycles at oocyte recovery day
Time frame: 2-4 weeks after randomization
Cycle cancellation rate
number of cancelled cycles during COS (no response), at OPU (premature ovulation, absence or degradation of COCs), during in vitro cultivation (fertilization failure, inadequate embryo quality) or due to other reasons (adverse events, ovarian hyperstimulation syndrome (OHSS), withdrawal)
Time frame: 6-7 weeks after randomization
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Frequency of side reactions
number of patients with local reactions (redness, itching, swelling or pain) or abdominal discomfort evaluated using visual analogue scale at the end of COS and at ET day
Time frame: 2-4 weeks after randomization
Implantation rate
ratio of the number of intrauterine gestational sacs to the number of transferred embryos
Time frame: 3-4 weeks after ET
Clinical pregnancy rate
presence of intrauterine gestational sac at transvaginal ultrasound measured per embryo transfer
Time frame: 5-6 weeks after randomization